Pores in the Wall: Claudins Constitute Tight Junction Strands Containing Aqueous Pores

In vertebrates, tight junctions (TJs) play a central role in sealing the intercellular space in epithelial and endothelial cellular sheets (Schneeberger and Lynch 1992; Gumbiner 1993; Anderson and van Itallie 1995). Without TJs, these cellular sheets cannot function as barriers to establish compositionally distinct fluid compartments. To maintain homeostasis, various materials must be selectively transported across these cellular sheets. Two distinct pathways are known for this transport: the transcellular and paracellular pathways in which materials move across plasma membranes and TJs, respectively (Spring 1998; Fig. 1). The molecular machinery involved in transport through the transcellular pathway (i.e., channels, pumps, transporters, etc.) has been identified and well characterized in molecular terms. In sharp contrast, our knowledge regarding paracellular transport is limited mainly because of the lack of information on the molecular architecture of...